The Unit on Reproductive Endocrinology and Infertility, led by James Segars, investigates underlying causes and effectiveness of treatment for a variety of clinical reproductive disorders. Our efforts have been focused on uterine leiomyoma (commonly known as fibroids), endometriosis, and reproductive disorders leading to infertility. The unit has the mission to conduct basic, translational, and clinical studies of importance to reproduction in the context of the multi-institutional clinical training program in Reproductive Endocrinology and Infertility. In the past year, we expanded upon our observation that the extracellular matrix of uterine fibroids was abnormally-formed. Based on several studies, our research suggests striking similarities common to fibroid development, keloid formation and altered tissue repair. This has led to the hypothesis that the altered extracellular matrix of uterine fibroids may contribute to fibroid growth. We plan to examine whether compounds that interfere with formation of excessive extracellular matrix similar to that observed in fibroids may have clinical utility. Also in the past year we have concluded a large prospective, randomized, placebo-controlled trial of the selective estrogen receptor modular(SERM), raloxifene, for the treatment of endometriosis-related chronic pelvic pain. This study headed by Dr. Stratton revealed that treatment with raloxifene actually hastened the return to pain in women with endometriosis, indicating that raloxifene, contrary to predictions, was not beneficial in this patient group. Our basic science studies in collaboration with Drs. Chrousos and Kino have revealed that the proto-oncoprotein cloned in our laboratory, Brx, is required for glucocorticoid action in vivo in some instances. This important observation indicates that Brx has a role beyond estrogen action, as initially understood, and may influence the action of other nuclear receptors, suggesting a possible importance for Brx for hormone action in tissues outside the reproductive tract.